Dose Conversion and Titration with a Novel, Once-Daily, OROS® Osmotic Technology, Extended-Release Hydromorphone Formulation in the Treatment of Chronic Malignant or Nonmalignant Pain

Abstract

The objective of this open-label, repeated-dose, single-treatment, multicenter study was to evaluate the outcomes associated with a standardized conversion from prior opioid therapy to a novel, once-daily, OROS osmotic technology, extended-release (ER) hydromorphone formulation in an outpatient population with chronic malignant or nonmalignant pain. The study period was divided into 3 phases: the prior opioid stabilization phase (> or =3 days), the conversion and titration phase (3-21 days), and the maintenance phase (14 days). Patients were evaluated at 5 visits during the study period. Analgesic efficacy was measured using the Brief Pain Inventory (BPI). At baseline, patients were required to have daily oral morphine equivalent requirements of > or =45 mg. Prior oral or transdermal opioid therapy was converted to single daily doses of ER hydromorphone (8, 16, 32, and 64 mg tablets) at a 5:1 (morphine equivalent to hydromorphone) ratio. Immediate-release (IR) hydromorphone was given as rescue medication for breakthrough pain. Among the 445 patients who enrolled, 404 received the study medication. Of these, 73 (18.1%) had chronic malignant pain and 331 (81.9%) had chronic nonmalignant pain. Dose stabilization (defined as a 3-day period during which the total daily dose of ER hydromorphone remained unchanged and < or =3 doses of IR hydromorphone per day were required) was attained by 73.8% of patients (298/404), of whom 70.1% (209/298) were stabilized with < or =2 titration steps. The mean +/- standard deviation (SD) time to dose stabilization was 12.1 +/- 5.7 days (range of 3 to 33 days). The mean +/- SD final daily dose of ER hydromorphone was 63.4 +/- 129.2 mg. The mean +/- SD final daily dose of IR hydromorphone was 11.5 +/- 36.4 mg, and the mean +/- SD final number of daily doses of IR hydromorphone was 1.7 +/- 1.3. Intent-to-treat and completer analysis demonstrated significant improvements in BPI ratings from prior opioid therapy to the end of ER hydromorphone therapy (P < 0.01 for all pairwise comparisons). Adverse events were consistent with those expected of an opioid agonist in such a patient group, affecting primarily the gastrointestinal and central nervous systems. This uncontrolled study delineates a regimen by which patients with chronic malignant or nonmalignant pain can be readily converted from prior opioid therapy and titrated to an appropriate maintenance dose of ER hydromorphone. Controlled longitudinal studies are required to further evaluate the use of ER hydromorphone in patients with discrete chronic malignant or nonmalignant pain conditions.

High-amylose carboxymethyl starch matrices for oral sustained drug-release: In vitro and in vivo evaluation

“…Figure reproduced from (Palangio, Northfelt et al 2002) with permission from Elsevier Ltd. 28 Figure 1.7 Schematic representation of drug-release from hydrophilic polymer matrix tablets. 32 Figure 1.8 Fronts in the swelling process (swelling, diffusion and erosion) of hydrophilic matrices during drug-release.…”

“…This osmotically active bilayer core is enclosed in a semipermeable tablet shell membrane that is permeable to water but not the drug or osmotic components. As water is absorbed from the gastrointestinal tract at a rate determined by membrane properties and the osmolality of the core constituents, the push layer expands and presses on the drug layer, slowly releasing drug solution/suspension through a laser-drilled orifice in the tablet shell (Palangio, Northfelt et al 2002). Another important factor governing the drug-release rate from osmotic systems, besides the rate at which water is able to pass in through the membrane, is how quickly the drug solution/suspension can pass through the hole.…”

“…Since the osmotic gradient remains constant, osmotic pumps can give a theoretically zero-order release profile after an initial lag time, which then gradually falls to zero (Collett and Moreton 2002;Palangio, Northfelt et al 2002). With systems such as the osmotic pump, dissolution rate may be rendered independent of gastrointestinal variables, such as pH and viscosity (Gupta and Robinson 1992).…”

Use of OROS® hydromorphone in the treatment of osteoarthritis and osteoporosis: A pooled analysis of three non-interventional studies focusing on different starting doses

“…OROS ® hydromorphone (Jurnista®) is a once-daily, extended release hydromorphone formulation, fi rst launched in Germany in 2006. It uses the OROS ® push-pull osmotic technology and consists of an osmotically active bilayer core enclosed in a semi-permeable tablet shell membrane [7], designed to deliver medication at a controlled rate to provide analgesic coverage for 24 hours [8,9]. Th e bioavailability of hydromorphone from OROS ® hydromorphone is minimally aff ected by food [10] and alcohol [11].…”

“…Th e bioavailability of hydromorphone from OROS ® hydromorphone is minimally aff ected by food [10] and alcohol [11]. Th e clinical effi cacy and safety of OROS ® hydromorphone are supported by data from several clinical trials [7,[12][13][14][15][16]. OROS ® hydromorphone is available in the United States, Canada, Turkey, Korea, Mexico, Brazil, Germany, Spain, Italy, and several other European countries.…”